BclAF1 Restriction Factor is Neutralized by Proteasomal Degradation and MicroRNA Repression During Human Cytomegalovirus Infection

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 May 31

PMID 22645331

Citations 49

Authors

Song Hee Lee

Robert F Kalejta

Julie Kerry

Oliver John Semmes

Christine M OConnor

Zia Khan

Benjamin A Garcia

Thomas Shenk

Eain Murphy

Affiliations

Soon will be listed here.

Abstract

Cell proteins can restrict the replication of viruses. Here, we identify the cellular BclAF1 protein as a human cytomegalovirus restriction factor and describe two independent mechanisms the virus uses to decrease its steady-state levels. Immediately following infection, the viral pp71 and UL35 proteins, which are delivered to cells within virions, direct the proteasomal degradation of BclAF1. Although BclAF1 reaccumulates through the middle stages of infection, it is subsequently down-regulated at late times by miR-UL112-1, a virus-encoded microRNA. In the absence of BclAF1 neutralization, viral gene expression and replication are inhibited. These data identify two temporally and mechanistically distinct functions used by human cytomegalovirus to down-regulate a cellular antiviral protein.

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